RAPID COMMUNICATION Modulation of Motoneuron Excitability by Brain-Derived Neurotrophic Factor MICHAEL GONZALEZ AND WILLIAM F. COLLINS, III Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York 11794-5230 Gonzalez, Michael and William F. Collins, III. Modulation of whereas Type S motoneurons are able to dictate motor unit motoneuron excitability by brain-derived neurotrophic factor. J. contractile speed via an orthodromic mechanism ( for review, Neurophysiol. 77: 502–506, 1997. The influence of neurotrophins see Mendell et al. 1994). on motoneuron survival and development has been well docu- Recently, it has been hypothesised that two members of the mented in cell cultures and neonates. In the present study, the role nerve growth factor family of neurotrophins, brain-derived neu- of brain-derived neurotrophic factor ( BDNF ) in the maintenance rotrophic factor (BDNF) and neurotrophin-4 (NT-4) act as mus- of motoneuron electrical properties was investigated. In adult male cle-derived neurotrophic factors for motoneurons (Funakoshi et rats, BDNF- or saline-saturated gelfoam was inserted between the al. 1993; Koliatsos et al. 1993). Both are produced by skeletal medial and lateral heads of the gastrocnemius muscles. After 5 muscle (Funakoshi et al. 1993; Koliatsos et al. 1993) and can days survival, in vivo intracellular recordings were obtained, and motoneuron biophysical properties were measured. In BDNF- be retrogradely transported by motoneurons (Koliatsos et al. treated rats, significant decreases in mean rheobase and in total 1993; Yan et al. 1993). Further, BDNF has been shown to cell capacitance of medial gastrocnemius motoneurons were ob- rescue motoneurons from programmed or injury-induced cell served. In addition, a concommitant increase in input resistance death during development (Oppenheim et al. 1992; Sendtner et and decrease in membrane time constant were noted in BDNF- al. 1992; Yan et al. 1993). The present study addresses the treated rats but were not statistically significant. No significant possible role of muscle-derived BDNF in the regulation of moto- treatment effect was observed in motoneuron conduction velocity, neuron electrical properties and is prompted by the observations action potential amplitude, equalizing time constant, electrotonic that BDNF mRNA expression is upregulated in medial gastroc- length, afterhyperpolarization amplitude and duration, and mem- nemius muscle following denervation (Funakoshi et al. 1993; brane potential sag during current injection. The observed changes Koliatsos et al. 1993). The results indicate that application of in motoneuron rheobase and total cell capacitance suggest that application of BDNF produces an increase in motoneuron excitabil- BDNF to the medial gastrocnemius muscle produces a signifi- ity coincident with a reduction in size. These data are discussed cant increase in electrical excitability of medial gastrocnemius with respect to the possible role of BDNF as a muscle-derived motoneurons. These data have been previously reported in ab- trophic factor for the regulation of motoneuron excitability. stract form (Gonzalez and Collins 1995). METHODS INTRODUCTION Data obtained from 94 medial gastrocnemius motoneurons in 18 The electrical properties of hindlimb motoneurons vary male Sprague-Dawley rats (350–450 g), anesthetized with a mix- systematically across motoneurons innervating different ture of ketamine/xylazine (90 and 10 mg/kg im, respectively), are included in the present report. The rats were assigned to one muscles as well as those innervating different motor units of three treatment groups (6 rats/group): BDNF 8 mg/ml, BDNF within the same muscle. Within a population of homony- 16.6 mg /ml, and saline control. The treatments were administered mous motoneurons, rheobase, input resistance, conduction via a 75 mm 3 piece of gelfoam (Upjohn) saturated with 50 ml of velocity, and size all covary with motoneuron type recruit- either BDNF (in phosphate buffered saline, pH 7.0) or saline and ment order and with motor unit contractile properties ( Flesh- inserted into the popliteal fossa of the left leg between the heads man et al. 1981; for review, see Binder et al. 1996). In of the lateral gastrocnemius and medial gastrocnemius muscles. cats, small, low rheobase, high-input resistance triceps surae After 5 days survival, the animals were prepared for in vivo intracel- motoneurons innervate slow-twitch muscle fibers ( Type S lular recording. Each rat was reanesthetized, and the lumbar enlarge- motoneurons) and are recruited first. Type F motoneurons, ment of the spinal cord was exposed via a laminectomy from vertebrae T 13 –L 3 . The dura was opened and the lumbo-sacral dorsal roots cut which are typically large, high rheobase and low-input resis- bilaterally. The left hindlimb was elevated, the medial gastrocnemius tance motoneurons, innervate fast-twitch muscle fibers and muscle was exposed, and the location of the gelfoam was determined are recruited later. Numerous studies have addressed the by visual inspection. In two rats, the gelfoam was displaced, and the question of how this organization is established and main- electrophysiological data obtained from those animals are not included tained, and there is compelling evidence to support the hy- in the present report. The medial gastrocnemius nerve was isolated pothesis that both orthograde and retrograde interactions be- and placed in continuity on bipolar platinum electrodes for stimulation tween motoneurons and the muscle fibers they innervate and recording. Fine-tipped glass microelectrodes (10–15 MV) filled underlie the differential distribution of motoneuron electrical with 3 M K acetate were used to locate and impale motoneurons. properties. Specifically, slow muscle fibers appear to exert Throughout each experiment, the rat was respirated artificially, and end-tidal CO 2 was monitored and maintained at 30–35 mm Hg. An a retrograde influence on motoneuron electrical properties, 502 0022-3077/97 $5.00 Copyright  1997 The American Physiological Society J-475-6RC / 9k0b$$ja23 08-13-97 18:06:09 neupa LP-Neurophys by 10.220.33.5 on November 17, 2017 http://jn.physiology.org/ Downloaded from